Welcome to the AML17 Trial Website

Registered Trial Centre staff can now
log in to the Online
Trial system. This Clinical Trial software is a unique
secure interface for patient data entry and drug randomisation.

News & Information

Limited reopening of APL randomisation

We are happy to announce that the APL randomisation has been reopened in a
restricted number of centres; owing to stock availability from Cephalon/TEVA we
are unfortunately not able to open the randomisation in all centres. Centres who
already have a supply of Arsenic Trioxide, or who have been notified by the
Trials Office that they are able to reopen the randomisation will be able to
recommence recruitment once the Principal Investigator, Pharmacist and Rsearch
Nurse have all attended a brief Webex initiation. For further details of
initiations, to inform us that you have stock on site, or for the centres
nearest you who are currently open, please contact the
Trials Office.

All other patients, and all other randomisations remain unaffected. All
centres will be required to attend a brief Webex trial refresher; for further
details please contact the trials office.

Version 7 of protocol now available

Following recruitment to target of the induction Mylotarg
randomisation, we have introduced a new protocol. In induction, it
is evaluating DA chemotherapy with daunorubicin given at one of two
doses (90mg vs 60mg) in Course 1. The amendment also includes an
opportunity to evaluate Arsenic levels in patients with APL, and a
changed starting dose of Everolimus (from 10mg to 5mg initially,
with possible dose escalation). Patients with Core Binding Factor
Leukaemia, who satisfy the relevant liver function eligibility
criteria, are eligible to receive Mylotarg at 3mg/m2 in Course 2 –
please contact the HCTU (029 2074 6413) to arrange for drug to be
shipped. Additionally, non-CBF patients with less than a 50%
reduction in blasts following course 1 are now reclassified as high
risk and can enter that randomisation irrespective of risk score,
assuming that they are not already in the FLT-3 inhibition
randomisation. Documentation was sent to sites in August/September
2011 to allow the amendment to be passed by R&D Offices.

Please note that entry into Version 5 of the protocol
is no longer possible.

Sites who have approved Version 7 of the protocol will be
notified by email once their approval has been processed by the
Trials Office. If you have not received this notification, or
require further assistance in processing the new amendment please
contact the Trial Office (029 2068 7464).

Clofarabine For “Off Protocol” Patients.

Patients in AML17 who are refractory to 2 courses of induction
therapy, or who relapse (having not already entered the high risk
randomisation) are eligible for the high risk randomisation within
AML17.

For relapsed or refractory patients who have been in an NCRI AML
Trial but are not entering the AML17 high risk arm, there is the
option to treat with schedules including Clofarabine at a discounted
price.

Older patients who have previously been treated in AML14 or
AML16, and who have relapsed, can also access Clofarabine.

If investigators wish to pursue this option please
use the following form to initiate a discounted supply, and/or
contact one of the regional representatives listed:

Trial Summary (Version 7)

Through the use of a risk based approach AML17 will evaluate
several relevant therapeutic questions in acute myeloid leukaemia
(AML) as defined by WHO, and high risk Myelodysplastic Syndrome. The
trial is open to all patients aged 18 to 60 years, and also to
patients aged 60 years or over for whom intensive therapy is
considered appropriate. At least 2800 patients will be recruited.
For patients who do not have the Acute Promyelocytic Leukaemia (APL)
subtype, an induction randomisation will compare DA
chemotherapy with daunorubicin given at one of two doses (90mg vs
60mg) in course 1 of induction. Consolidation will compare
one course with two courses of high dose Ara-C treatment.

After course 1 of treatment, patients will be segregated based on
their molecular-genetic characteristics, and a validated risk score.
Patients who have a FLT3 mutation will be randomised to receive, or
not, the FLT3 inhibitor CEP-701 after each
subsequent chemotherapy course. Patients not in this randomisation
who are at high risk of relapse based on the AML Risk Score, or who
have less than a 50% reduction in blasts following course 1, will be
eligible for an allogeneic stem cell transplant if a donor is
available, and/or enter a study of a novel combination. These
patients will be randomised between FLAG-Ida
(standard arm) vsDaunorubicin/Clofarabine
with the aim of maximising the number of patients receiving an
allogeneic transplant.

Patients who have Core Binding Factor (CBF) i.e.
favourable risk disease leukaemia will be randomised only to the 3
versus 4 comparison. They are also eligible to receive Mylotarg with
Course 2 of chemotherapy subject to fulfilling hepatic criteria. The
rest of the patients will be randomised to receive, or not, up to
twelve treatments with the mTOR inhibitor,
Everolimus in combination with chemotherapy.

For patients with APL, the Italian AIDA
anthracycline plus ATRA based chemotherapy approach will be compared
with the chemotherapy-free combination of ATRA plus Arsenic
Trioxide.

At diagnosis, material will be sent to reference labs for
molecular and immunophenotypic characterisation and the
identification of markers of minimal residual disease (MRD)
detection. The predictive value of these markers will be validated
in the early part of the trial, and the clinical impact of this
information will be tested in a randomised fashion in a later
patient cohort.

AML17 has been given approval by Wales MREC. Centres should either
have received or will shortly received materials to allow them to
get the trial approved at their own centres. Copies of useful
documentation are in the downloads section of the website.

For more information about the trial, please contact the Trials
Office in Cardiff on 029 2068 7464.